a study of two fabrazyme (agalsidase beta) dosing regimens in treatment-naïve, male pediatric patients without severe symptoms

Conditions: Fabry Disease

Summary: the purpose of this study was to determine whether 2 alternative dosing regimens of fabrazyme (agalsidase beta) (1.0 mg/kg every 4 weeks or 0.5 mg/kg every 2 weeks) were effective in treatment-naïve pediatric participants without severe symptoms. participants were to be treated for 5 years.


Eligibility criteria:
inclusion criteria: * the participant and/or participant's parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed. * the participant must had a confirmed diagnosis of fabry disease as documented by leukocyte α-galactosidase a (αgal) activity of \<4 nmol/hr/mg leukocyte (preferred assay; resulted from a central laboratory). if the leukocyte αgal activity assay was difficult to obtain, the participant might be enrolled based on documented plasma αgal \<1.5 nmol/hr/ml, with the agreement of the medical monitor (resulted from a central laboratory). * the participant must had evidence of globotriaosylceramide (gl-3) accumulation as documented by plasma gl-3 (\>7.0 µg/ml) or urinary gl-3 (\>0.3 mg gl-3/mmol creatinine) levels (results from a central laboratory). * the participant must be male ≥5 and ≤18 years of age. exclusion criteria: * participant had albuminuria (first morning void urinary albumin/creatinine ratio \>30 mg/g on at least 2 out of 3 consecutive samples, each at least 1 week apart). * participant had a glomerular filtration rate (gfr) by iohexol \<90 l/min/1.73m\^2. in case of properly documented low protein intake, values as low as 80 ml/min/1.73 m\^2 might be acceptable, after consultation with the medical monitor. * participant had documented evidence of stroke or transient ischemic attack (tia), or if a brain magnetic resonance imaging (mri) had been performed, bright lesions \>2 mm on t2- or fluid attenuated inversion recovery (flair)- weighted images within the white matter or the basal ganglia. * participant had severe and recurrent acroparesthesia, judged by the physician as frequent (more than once a week) pain episodes for at least 3 months that influenced daily activities, irrespective of medication. * participant had an end-diastolic left ventricular posterior wall thickness (lvpwtd) and/or an end-diastolic interventricular septum thickness (ivstd)≥2 standard deviations (sd) compared to normal (based on body surface area \[bsa\] normal ranges from kampmann, et al 2000) as read at the study site. * participant had received prior treatment specific to fabry disease. * participant had participated in a study employing an investigational drug within 30 days of the start of their participation in this study. * participant had any medical condition or extenuating circumstance, which in the opinion of the study investigator, could interfere with study compliance. * participant had any medical condition or extenuating circumstance, for example diabetes mellitus, which in the opinion of the study investigator, could interfere with the interpretation of study results. * participant was on treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers (aceis/arbs). * participant had any contra-indication mentioned in the labeling of fabrazyme and/or iohexol (omnipaque). * participant or parent(s)/legal guardian(s) was unwilling to comply with the requirements of the protocol.

Keywords: α-gal, α-galactosidase-a, r-hαgal